BACKGROUND: Surgeon satisfaction and patient analgesia during the procedure of laparoscopic surgery are important issues. The aim of this work was to study if an intrathecal (IT) Bupivacaine combined with Magnesium sulfate may or may not provide good surgeon satisfaction in addition to improvement of intraoperative and postoperative analgesia. METHODS: Sixty female patients were enrolled in this prospective, randomized, double-blind controlled clinical trial study. All patients were operated for gynecological laparoscopic surgery under spinal anesthesia. Patients were divided into two groups (Bupivacaine and Magnesium). Group Bupivacaine (30 patients) received intrathecal Bupivacaine 0.5% only (15 mg), while 30 patients in group Magnesium received intrathecal Bupivacaine (15 mg) in addition to intrathecal Magnesium sulfate (50 mg). The sensory block level, the intensity of motor block, the surgeon satisfaction, the intraoperative visual analog scale (VAS) for pain assessment, the postoperative VAS, and side effects were recorded during the intraoperative period and within the first 24 hours after surgery in the post-anesthesia care unit. RESULTS: Surgeon satisfaction, intraoperative shoulder pain, postoperative pain after 2 h, and perioperative analgesic consumption (ketorolac) were significant better in group Magnesium than in group Bupivacaine. (P < 0.05). The onset of motor and sensory blocks was significant longer in group Magnesium than the other one. The incidence of PONV, pruritus and urinary retention was insignificant statistically between both groups. CONCLUSIONS: Magnesium sulfate if used intrathecally as an adjuvant to Bupivacaine would provide a better surgeon satisfaction and would improve the analgesic effect of spinal anesthesia used for gynecological laparoscopic surgery.
Analgesia* ; Anesthesia, Spinal ; Bupivacaine* ; Clinical Study* ; Female ; Gynecologic Surgical Procedures* ; Humans ; Incidence ; Intraoperative Period ; Laparoscopy ; Magnesium Sulfate* ; Magnesium* ; Pain Measurement ; Pain, Postoperative ; Postoperative Nausea and Vomiting ; Prospective Studies ; Pruritus ; Shoulder Pain ; Urinary Retention ; Visual Analog Scale

3-Bromopyruvate (3BP) is a new, promising anticancer alkylating agent with several notable functions. In addition to inhibiting key glycolysis enzymes including hexokinase II and lactate dehydrogenase (LDH), 3BP also selectively inhibits mitochondrial oxidative phosphorylation, angiogenesis, and energy production in cancer cells. Moreover, 3BP induces hydrogen peroxide generation in cancer cells (oxidative stress effect) and competes with the LDH substrates pyruvate and lactate. There is only one published human clinical study showing that 3BP was effective in treating fibrolamellar hepatocellular carcinoma. LDH is a good measure for tumor evaluation and predicts the outcome of treatment better than the presence of a residual tumor mass. According to the Warburg effect, LDH is responsible for lactate synthesis, which facilitates cancer cell survival, progression, aggressiveness, metastasis, and angiogenesis. Lactate produced through LDH activity fuels aerobic cell populations inside tumors via metabolic symbiosis. In melanoma, the most deadly skin cancer, 3BP induced necrotic cell death in sensitive cells, whereas high glutathione (GSH) content made other melanoma cells resistant to 3BP. Concurrent use of a GSH depletor with 3BP killed resistant melanoma cells. Survival of melanoma patients was inversely associated with high serum LDH levels, which was reported to be highly predictive of melanoma treatment in randomized clinical trials. Here, we report a 28-year-old man presented with stage IV metastatic melanoma affecting the back, left pleura, and lung. The disease caused total destruction of the left lung and a high serum LDH level (4,283 U/L). After ethics committee approval and written patient consent, the patient received 3BP intravenous infusions (1-2.2 mg/kg), but the anticancer effect was minimal as indicated by a high serum LDH level. This may have been due to high tumor GSH content. On combining oral paracetamol, which depletes tumor GSH, with 3BP treatment, serum LDH level dropped maximally. Although a slow intravenous infusion of 3BP appeared to have minimal cytotoxicity, its anticancer efficacy via this delivery method was low. This was possibly due to high tumor GSH content, which was increased after concurrent use of the GSH depletor paracetamol. If the anticancer effectiveness of 3BP is less than expected, the combination with paracetamol may be needed to sensitize cancer cells to 3BP-induced effects.
Acetaminophen ; therapeutic use ; Adult ; Carcinoma, Hepatocellular ; Disease Progression ; Drug Therapy, Combination ; Enzyme Inhibitors ; Glutathione ; Glycolysis ; Hexokinase ; Humans ; L-Lactate Dehydrogenase ; Lactic Acid ; Lung Neoplasms ; secondary ; Male ; Melanoma ; drug therapy ; Necrosis ; Neovascularization, Pathologic ; Pleural Neoplasms ; secondary ; Prognosis ; Pyruvates ; adverse effects ; therapeutic use ; Treatment Outcome

Objective To explore the in vivo anticancer, anti-angiogenesis and immunomodulatory efficacies of the bioactive polysaccharide isolated from cold aqueous extract of Jania rubens (JCEM) and Pterocladia capillacea (PCEM) as well as hot aqueous extract of Enteromorpha intestinalis (EHEM) against hepatocellular carcinoma rat model (HCC) and to study their chemical composition. Methods The sugars and amino acids composition of the bioactive polysaccharides of JCEM, PCEM and EHEM were determined using gas liquid chromatography and amino acid analyzer, respectively. These polysaccharide extracts (20 mg/kg b.wt. for 5 weeks) were assessed on hepatocarcinogenesis in rats and α-fetoprotein (AFP), carcinoembryonic antigen (CEA), glypican-3 (GPC-3), hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF) and Ig G levels were evaluated. Results The GLC analysis of JCEM, PCEM and EHEM polysaccharide revealed the presence of 10, 9 and 10 sugars, in addition the amino acid analyzer enable identification of 16, 15 and 15 amino acids, respectively. These polysaccharide extracts of JCEM, PCEM and EHEM produced significant decrease in serum AFP, CEA, GPC-3, HGF and VEGF compared with untreated HCC group. JCEM, PCEM and EHEM had an immunostimulatory responses by increasing the IgG levels as compared by naïve value (1.23, 1.53 and 1.17 folds), respectively. The bioactive polysaccharides in HCC induced rats improved the humoral immune response. The photomicrographs of liver tissue sections of the groups of HCC treated with polysaccharide extracts of Jania rubens and Enteromorpha intestinalis showed intact histological structure. Moreover, fractions HE1, HE4, HE7 obtained from polysaccharide of EHEM showed moderate cytotoxic activity against HepG2 in vitro with IC